Objective:To investigate the expression of sphingosine kinase 1 (SphK1) and its clinical significance in breast invasive ductal carcinoma ( BIDC).Methods: We detected SphK1 expression in 58 samples of surgically resected paired BIDC and normal tumor-adjacent tissues samples by using immunohistochemistry.The correlation between SphK 1 expression and clinicopathologic features was analyzed.Results: The positive expression rate of SphK 1 in BIDC tissues was 69.0% ( 40/58 ) , while its positive expression rate in normal tumor-adjacent was 17.2% (10/58),the difference was statistical significance (χ2=31.636,P=0.000). Clinicopathological evaluation suggested that SphK 1 positive expression was associated with ER negative (χ2=4.392,P=0.036),PR negative (χ2=7.920 , P=0.005 ) , lymph node metastasis (χ2 =5.033 , P=0.025 ) and tumor stage (χ2 =7.117 , P=0.008 ) . Conclusion:The high-expression of SphK1 is correlated with the poor clinicopathological features in BIDC ,suggesting SphK1 may play a key role in development and progression of BIDC.

[摘 要] 目的：探讨紫甘薯花色苷（purple sweet potato anthocyanin, PSPA）是否通过circ_0003998/miR-145轴调控乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。方法：选用乳腺癌MDA-MB-231细胞，将其分为对照组，200、400和800 μg/ml PSPA组，pcDNA组、pcDNA-circ_0003998组、si-NC组、si-circ_0003998组、si-circ_0003998+anti-miR-145组、PSPA+pcDNA组、PSPA+pcDNA-circ_0003998组和PSPA+anti-miR-145组。用qPCR法检测细胞中circ_0003998和miR-145的表达，CCK-8法、Transwell小室法分别检测转染前后细胞的增殖、迁移和侵袭能力，WB法检测细胞中Ki-67、MMP-2和MMP-9蛋白的表达。用双荧光素酶报告基因实验验证circ_0003998与miR-145的靶向关系。结果：与对照组比较，各剂量PSPA组MDA-MB-231细胞的增殖抑制率、miR-145表达水平均显著升高（均P<0.01），Ki-67、MMP-2、MMP-9蛋白和circ_0003998的表达水平、细胞迁移和侵袭细胞数均显著降低（均P<0.01），并呈现浓度依赖性。circ_0003998可以靶向负调控miR-145的表达。敲减circ_0003998后，MDA-MB-231细胞的增殖抑制率、miR-145表达水平显著升高，Ki-67、MMP-2和MMP-9蛋白表达水平、细胞迁移和侵袭细胞数均显著减少（均P<0.01）。共转染si-circ_0003998和anti-miR-145则可逆转敲减circ_0003998表达对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用，过表达circ_0003998或抑制miR-145表达可逆转PSPA对MDA-MB-231细胞增殖、迁移和侵袭的抑制作用。结论：PSPA通过circ_0003998/miR-145轴抑制乳腺癌MDA-MB-231细胞的增殖、迁移和侵袭。